Diisopropylethylamine → Biotin-PEG2-NH-Boc

HRID 587899Notes

Reaction equation

HRID 587899 reaction equation
[CH2:1]1[S:5][C@@H:4]([CH2:6][CH2:7][CH2:8][CH2:9][C:10]([OH:12])=O)[C@H:3]2[NH:13][C:14]([NH:16][C@@H:2]12)=[O:15].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.CCN(C(C)C)C(C)C.[C:50]([NH:57][CH2:58][CH2:59][O:60][CH2:61][CH2:62][O:63][CH2:64][CH2:65][NH2:66])([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51]>CN(C=O)C>[C:50]([NH:57][CH2:58][CH2:59][O:60][CH2:61][CH2:62][O:63][CH2:64][CH2:65][NH:66][C:10](=[O:12])[CH2:9][CH2:8][CH2:7][CH2:6][C@H:4]1[C@@H:3]2[C@@H:2]([NH:16][C:14]([NH:13]2)=[O:15])[CH2:1][S:5]1)([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 171548BiotinHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 9881394tert-butyl N-{2-[2-(2-aminoethoxy)ethoxy]ethyl}carbamate

Product 1

HCID 10600603Biotin-PEG2-NH-BocYield 90%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of vitamin H (Biotin) (2.2 g, 9 mmol), O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HBTU) (3 g, 8 mmol), and DIPEA (1.8 mL, 10 mmol) in DMF (100 mL) was stirred for 10 minutes at room temperature before being adding dropwise to a solution of N-Boc-3,6-dioxaoctane-1,8-diamine (1.5 g, 6 mmol, 1). The reaction mixture was stirred for 1 hour at room temperature, after which the DMF was removed in vacuo to give an oily residue, which was purified by flash silica gel column chromatography (CH2Cl2/CH3OH, 25/1, v/v) to afford N-Boc-N′-biotinyl-3,6-dioxaoctane-1,8-diamine (2.0 g, 90%). 1H NMR (300 MHz, CD3OD): δ 4.5 (m, 1H), 4.3 (m, 1H), 3.6 (s, 4H), 3.54 (tt, 4H), 3.39 (t, 2H), 3.26 (t, 2H), 2.9 (dd, 1H), 2.7 (d, 1H), 2.2 (t, 2H), 1.7-1.5 (m, 8H), 1.4 (s, 9H); MALDI HRMS: m/z 497.2416 [M+Na+]. Calcd for C21H38N4NaO6S 497.2410.

Workup

  1. customafter which the DMF was removed in vacuo
  2. customto give an oily residue, which
  3. customwas purified by flash silica gel column chromatography (CH2Cl2/CH3OH, 25/1

Sources & evidence

ORD record
ord-58504ee295924edca60e66e875673844
Source dataset
uspto-grants-2016_01
Patent number
US09227943B2

Reaction notes

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